Dr. Maier plans an extensive and broad research program which will attempt to provide an integrated understanding of how stress impacts on measures of the immune system at the behavioral, physiological and immunological levels. Two stressors, inescapable shock and defeat, will be utilized and in vivo changes in immune function will be studied. The first set of studies will focus on the behavioral factors which are important in determining whether and how stressor exposure will alter the development of antibodies and antibody (Ab) secreting cells to the antigen (Ag) KLH. The research will focus on behavioral controllability of the stressor and dominance. The second set of studies will focus on the neural and neuroendocrine mediators by which the stressors alter Ab levels. This will include noradrenergic processes associated with the paraventricular nucleus (PVN). The applicant hypothesizes that activation of this area is central to the alteration of Ab levels to Ag administered before the stressor. In addition, he will consider peripheral neuroendocrine mediators and focus on corticosteroids and catecholamines. The third set of studies are focussed on on immunology with a consideration of neural and neuroendocrine effects of the stressors on alterations in cell trafficking between immune compartments leading to changes in cell types in the lymphoid compartments which in turn lead to Ab alterations. These studies will involve the use of about 2,000 male Holtzman Sprague-Dawley rats per year.